Adeel ShafiView profile/website
Ultrasound imaging is a real-time imaging technique that is non-invasive, doesn’t produce any ionising radiation, and is one of the most commonly used imaging modalities in the clinic today. The use of ultrasonic contrast agents, known as microbubbles, significantly enhances imaging of the vasculature and they now have the potential to be developed as drug/gene delivery vehicles for site-specific diagnosis and therapeutics.
During imaging, the sound energy is attenuated, scattered and reflected as it travels through the body and interacts with the different interfaces. And the strength of the received signal from this dictates the level of grey-scale contrast seen on the ultrasound image. To enhance image acquisition, microbubbles have been produced. These bubbles, which are around the same size as red blood cells have the unique ability to pulsate when sonicated, which in-turn enhances the contrast seen in real-time images of the vasculature.
In order to manufacture clinically translatable theranostic microbubbles, it is imperative to understand the mechanical and nanostructural properties of these agents; this will enrich the understanding of how the structural, biophysical and chemical properties of these bubbles impact their functionality. My project, which brings together biology and physics from across the School of Engineering and Centre for Cardiovascular Science at Edinburgh University, is primarily focussed on the systematic characterisation of our own microbubbles. By using atomic force microscopy along with other complex characterisation techniques we can further understand their mechanical and nanostructural properties, knowledge which can be applied to enhance their performance in biomedical (diagnostic and therapeutic) application. In the secondary part of my project I am functionalising the microbubbles for targeting specific markers of cardiovascular disease, and conducting adhesion studies to assess the potential these microbubbles have in ultrasonic molecular imaging.
I chose to do my PhD as part of the Optima programme because of the inter-disciplinary research it so strongly promotes, I feel that to truly solve clinical problems it is imperative that all the science disciplines to come together. Through Optima I receive bespoke business training in health innovation and entrepreneurship, this is teaching me how to take a concept from the lab and commercialise it for solving real-world problems. It is an area I would not have been exposed to through a conventional PhD programme and am now extremely passionate about the commercialisation of science. It is vital that innovation is able to have an impact worldwide; through saving lives, reducing healthcare costs, improving diagnosis and enhancing delivery of therapeutic agents.
Anastasia KaparaView profile/website
Estrogen receptor (ER), is a transcriptional factor which is over-expressed in a variety of different cancers, including breast cancer. Although the treatment against ER overexpression is improving with less side effects, drug resistance remains one of the major clinical issues.
Overall, the aim of the project is to use sophisticated and sensitive technologies to address the molecular imaging of ER expression in breast cancer models. Determining the alterations in ER expression in response to novel anticancer drugs against breast cancer will lead to more effective drug selection, lower possibility of treatment failure and a clinically meaningful improvement in outcomes. Future prospective studies may involve long term monitoring of breast cancer patients, who are on endocrine therapy, by using a combination of molecular biology and nanotechnology for less invasive, targeted and rapid therapeutic approaches.
The OPTIMA programme places emphasis on interdisciplinary research as it combines the study of molecular interactions and structural dynamics with the development of a complete scientific business profile. I am confident that this PhD will improve my background knowledge and will contribute to achieve my personal goals which are to continue in the research field of molecular diagnosis and modern therapeutics.
Clara VergezView profile/website
Cardiovascular disease is the leading cause of death worldwide. Heart attacks occur when a blood clot blocks the coronary artery, restricting blood flow to the heart muscle. Atherosclerotic plaques in the coronary artery walls cause heart attacks when they rupture and expose their pro-coagulant contents to the blood supply, forming a clot.
Research in the field currently focusses on detecting plaques which are prone to rupture (i.e. “vulnerable plaques”) in the hope that removing them from patients with coronary artery disease will lower their risk of heart attack. OCT (optical coherence tomography) is a relatively new medical imaging technique enabling precise visualisation of “vulnerable plaque” morphology (such as a thin fibrous cap, a lipid core, calcifications) in a similar way to ultrasound, using light instead of sound to create an image of the tissue. However, one key feature yet to be made visible with OCT is macrophage infiltration into the cap of the plaque.
Preliminary studies have shown that macrophage visualisation within plaques may be possible with OCT and my thesis project aims to enhance this visualisation. Along the course of my project I will be working on in vitro models (a model “phantom” artery and ex-vivo human arteries), in vivo animal models as well as a human clinical trial. If we can enhance the detectability of macrophages within atherosclerotic plaques with OCT we could potentially distinguish vulnerable plaques from non-vulnerable ones and thus vulnerable patients from non-vulnerable ones!
I came across OPTIMA completely by chance when I had not yet started my search for PhDs and I was hooked when I heard about their aims and ideals. Most importantly for me, all the projects having an optical medial imaging component are very clinically relevant and many boast a "bench to bedside" philosophy. The added interdisciplinary component is what makes this PhD program unique, perhaps more challenging but certainly fun! And finally the taught entrepreneurship component of the OPTIMA program teaches us the importance of knowing how to commercialise science, a invaluable skill for our future careers, whatever they may be...
Dawn GilliesView profile/website
Real-time and non-invasive measurements of pancreatic ductal adenocarcinoma mechanical properties with quantitative phase imaging.
Pancreatic ductal adenocarcinoma (PDAC) is currently a devastating diagnosis. There is only a 3.3% chance of surviving five years from diagnosis. It is a cancer characterized by dense, fibrous tissue. Significant changes occur in the mechanical properties at both cellular and tissue level. Further knowledge and understanding of the influence of proteins on the mechanical properties of PDAC is needed to improve treatment options.
We have created novel optical imaging methods which allow us to perform measurements in real time and non-invasively in a 3D complex environment which overcome the disadvantages of the current state of the art to investigate the mechanical properties of cells and tissues in environments which closely mirror the tumour niche.
I applied to the OPTIMA CDT as I can benefit from interdisciplinary supervisors and research, and I can combine my PhD with training in business and entrepreneurship. It is especially useful in biomedical research as it can help make the translation from scientific research to a clinical device which can have a positive impact on public health.
Gillian CraigView profile/website
Cancer is a major cause of death worldwide and the majority of deaths are due to diagnosis at advanced stages when the cancer has metastasised. There is the need for more efficient cancer screening methods to improve patient survival. Cancer cells have a very different gene expression from healthy cells therefore mRNA biomarkers would be of great use for early detection.
My project is based at the Photophysics department at the University of Strathclyde where I am working to develop gold nanorod probes for the detection of cancer specific mRNA. Nanotechnology is new and exciting interdisciplinary field that combines engineering, physics, chemistry, biology and medicine. It has a huge potential for medical applications in the diagnosis and personalised treatments of human diseases. Nanoparticles such as gold are of particular interest in biological imaging due to the unique optical properties they possess.
The project aims to design gold nanorods functionalised with a DNA sequence that is complementary to the target mRNA and will also be conjugated to a fluorophore. This creates a probe that will emit a fluorescent signal once bound to its target. Fluorescence techniques will be used to characterise the probe as well as imaging techniques to study the probe in a cellular environment. A gold nanorod imaging probe has the potential to provide a non-invasive blood sample test which could provide early diagnosis of aggressive cancers.
My background is in cancer biology and I wanted to stay in this area while learning new skills to apply research that is clinically relevant. I chose the OPTIMA programme because of the unique training it offers. The exposure to innovation and business processes as well as the clinical and industrial placements really appealed to me, as well as the collaborative aspect of the project. I believe taking expertise from different disciplines will greatly strengthen the project.
Hazel StewartView profile/website
Surgery is one of the primary treatment options for cancer alongside chemotherapy and radiotherapy. While there are many imaging techniques that play important roles in preoperative cancer diagnostics, very few can be applied intraoperatively to aid surgeons in distinguishing tumour margins.
Fluorescence techniques offer a less costly and less disruptive alternative to traditional imaging methods for surgery; however there are currently a limited number of fluorophores that have been FDA approved as fluorescence imaging contrast agents for use in fluorescence guided surgery.
Based in the Photophysics Group at Strathclyde, this project will involve the investigation of the properties of both intrinsic and extrinsic fluorophores that have been identified as potential candidates for use in fluorescence guided surgery. Further to this, the implementation of a liquid light guide based fluorescence system will be tested, and medical applications outside of cancer surgery will also be investigated for these fluorophores.
OPTIMA offers a unique opportunity to develop interdisciplinary skills. As my background has a strong focus on physics, this programme offered the perfect opportunity for me to develop my skills in areas such as biology and chemistry, whilst contributing to meaningful research.
Lung cancer is the most common cause of cancer related deaths worldwide and many patients live for less than 12 months after diagnosis. This is often because patients are diagnosed with advanced/late stage disease. It is challenging to improve survival times because the earliest stages of lung cancer are difficult to definitively diagnose using simple non-invasive tests.
The aims of my research are to validate pre-existing and novel imaging agents for lung cancer. This work, along with that of a large team of biologists, chemists, physicists and medical doctors has the potential to lead to exciting developments in how lung cancer patients are diagnosed. The overall aims of our team are the produce and test fluorescence and radioactive probes which can be administered to patients. These probes interact with parts of cancer cells causing them to 'light up' on tests such as PET scans. This information can help doctors to detect where cancers are in the body, how far the cancer has spread and might provide information about how best to treat each individual lung cancer patient.
Jamie ScottView profile/website
Granzyme B is the signature enzyme of choice for CD8+ T Cells in our immune systems response against foreign bodies. CD8+ T Cells form a major part of the adaptive immune system and without their effector activity we would succumb to many infections and diseases. The activity of these cells is kept under control by T regulatory cells (Tregs) which are able to suppress function of CD8+s when required, in order to prevent autoimmune diseases.
Patients suffering from cancer have the ability to draw large numbers of CD8+ cells with specificities to tumour antigens to the TM. Therefore, in theory, these T cells should be able to mediate clearance of malignant cells in much the same manner as invading microbes/bacteria. However, in cancer patients these T cells are unable to eradicate the tumour because of an increasing number of CD4+ CD25+ Foxp3+ Tregs found in the TM. As previously described, Tregs have the capability to suppress the immune system, however, in the presence of malignant cells they should not suppress the immune response to such an extent that tumours can thrive. As such, the increasing ratio of Tregs:CD8+ T cells results in a worse prognosis and leads to development of tumour tolerance rather than tumour clearance. However, crucial questions remain unanswered: 1) what are the specific signals / molecules that give rise to an elevated number of Tregs in the TM, and 2) how Tregs suppress CD8+ T cell cytotoxicity in vivo.
In order to answer these questions my research combines both organic chemistry and immunology through the development of a fluorescent probe specific for CD8+ T Cells by labelling Granzyme B. Through fluorescence imaging of CD8+ T Cells in the TM we hope to address some of the previously unanswered questions.
Katie EmberView profile/website
Cholangiocarcinoma is a cancer of the bile duct that also affects the liver. Very little is known about the molecular basis for the disease and it has an extremely low survival rate – 95% of cases are fatal within 5 years. However, this could be significantly improved by novel diagnostic technologies. Raman spectroscopy is an optical technique capable of discriminating between tissue samples based on their molecular composition.
Raman spectroscopy has proven a promising tool for cancer diagnosis and surgery but has never been applied to cholangiocarcinoma.
I’m working with both the Campbell group of the School of Chemistry and the Forbes group of the Centre for Regenerative Medicine to develop Raman spectroscopy as a new way for sensing cholangiocarcinoma early and accurately. Such a tool could be implemented in diagnosis, surgery and investigating the efficacy of therapeutic drugs on cholangiocarcinoma. It could also greatly assist the elucidation of the underlying biomolecular mechanisms of this disease.
Optical medical imaging is where biology, chemistry and physics converge, and I’ve always found it difficult to choose one of the three sciences to focus on – they are all equally fascinating and many new technologies are arising from the conjunction between them. The interdisciplinary nature of the OPTIMA programme means that there are endless opportunities to learn new techniques and ways to approach problems, and Edinburgh and Glasgow are both fantastic places to do a PhD!
Kirsty CallanView profile/website
The mineralocorticoid aldosterone plays a key role in sodium transport via the mineralocorticoid receptor (MR). Glucocorticoids and mineralocorticoids have similar affinity for the MR, which can result in overstimulation of the receptor since glucocorticoids are present at much higher levels. This problem is avoided by the presence of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2) which deactivates glucocorticoids.
However, mutations can cause a lack, or inactivity, of HSD2. Lack of HSD2 results in a condition known as the syndrome of apparent mineralocorticoid excess (SAME) which is usually fatal in childhood. Deficiency of the enzyme has been shown to cause salt-sensitive hypertension. Currently, there is no clinical diagnostic test for HSD2 levels.
Nanoparticles are particles with at least one dimension less than 100nm. They have unique optical properties which make them useful in diagnostics. In particular, they can be used to increase the sensitivity of Raman spectroscopy by adsorbing the sample onto nanoparticles resulting in an enhanced signal (surface enhanced Raman spectroscopy). Furthermore, they can be functionalised with recognition molecules, such as DNA, for specific detection.
The aim of my project is to develop an assay for the detection of HSD2 mRNA based on nanoparticles and Raman spectroscopy. I was drawn to the OPTIMA program as I believe that the multidisciplinary nature of the program makes it different from other PhD programs and will be invaluable for a career in research.
Lana WoolfordView profile/website
My project is centred around the creation of a diagnostic tool for cervical cancer which is automated, inexpensive and based on the ‘molecular pathology’ of the samples used. This is to try and improve the timing and accuracy of diagnosis for patients, and also to reduce the burden of manual diagnosis for clinicians.
The project will involve looking at two different methods of using the optical scattering technique Raman spectroscopy to analyse the biochemical makeup of cells from the cervix.
The first method is the global approach, where all the biochemical differences between normal and cancerous samples are considered. This will be done using wavelength-modulated Raman spectroscopy (WMRS) to probe the vibrational energy levels of molecules in the sample, and does not require any major sample preparation. The second method is the targeted approach, where a specific marker for the cancer in question (such as an increase in the production of a particular protein) is measured in each sample. This will be carried out using surface–enhanced Raman spectroscopy (SERS). The Raman signal enhancement is provided by metal nanoparticles which have been tagged with an antibody to the protein being studied. The intensity of the Raman peaks for these ‘functionalised nanotags’ correspond to the levels of the target in the sample. The project will also look at how the Raman spectra can be automatically collected from thousands of cells in the same sample. Hopefully the final tool will improve cervical cancer diagnosis for patients and healthcare services alike.
Jee Soo (Monica) KimView profile/website
Multiple sclerosis (MS) is a chronic and complex debilitating neurological disorder caused by inflammation and the inability to repair the damage on myelin sheaths. Myelin sheaths are lipid-rich structures made by cells called oligodendrocytes in the central nervous system. These cells wrap around the axons of neurons, the key signalling cells of the nervous system, to provide nutritional support and allow fast signalling conduction.
MS cost the European economy €14.6 billion in 2010 alone with 540,000 sufferers. Current treatments are focused on dampening the damage and not enhancing their repair. My project is aimed at using medical optical imaging to create a high-throughput drug screening platform to find drugs that will enhance the repair of myelin sheaths in MS.
I joined the CDT OPTIMA programme because of its multi-disciplinary aspect. Although science is divided into different disciplines (biology, chemistry, engineering, physics, IT,…), I believe the best research is conducted when multiple, or even all, scientific disciplines are brought together. My project is allowing me to bring my biomedical sciences background to study the disease MS while incorporating the technology and knowledge from multiple other scientific disciplines. In addition, the programme is allowing the learning and development of how to take scientific ideas and research from the lab into the real-world, where they have the potential to make important societal impact.
Paul CowlingView profile/website
Worldwide, lung cancer killed more than 1.5 million people in 2015. It is the second most common form of cancer, with only 15% of patients alive five years after diagnosis. A prime reason for this harrowing statistic is many people are not diagnosed until the disease is advanced, when treatments for lung cancer become less effective. New techniques for early stage diagnosis are needed to increase earlier diagnoses and improve patient outcome.
I am developing new diagnostic tools which will allow for earlier detection of lung cancer, using bio-orthogonal reactions (reactions that can take place inside cells without interrupting normal biological processes). These reactions can be targeted so that they only occur inside cancer cells. I am using fluorescent probes that will be activated, or "switched on", by these bio-orthogonal reactions to image lung cancer cells. The benefit of using fluorescent probes is that the optical light emitted can be quantified in real time to visualise tumours. These new diagnostic tools are non-invasive, faster and more cost effective than current methods.
The primary benefit of working in the OPTIMA CDT is that I am part of a collaborative network of people who are constantly exchanging ideas. In addition, exposure to courses within the Business School helps improve my understanding of how to translate ideas to products for the general public.
Scott HoffmannView profile/website
My work involves the development of a novel molecular FRET probe to allow the investigation of protein dynamics in the cardiovascular system.
Tom SpeightView profile/website
Arguably the biggest global problem in medicine is the huge rise in antibiotic resistance. We use far too many antibiotics and it gives pathogens the opportunity to develop a resistance, eventually making the drugs against them useless. One of the reasons we’re overusing antibiotics is a lack of confidence in our current methods to diagnose infections, especially those in the lower airways of the lung such as pneumonia.
I’m working as a member of the Proteus research group, who are aiming to overcome these problems by developing an optical fibre-based imaging system, to be used in hospitals to image deep into the lung in real-time and at the bedside. My research will focus on the development and validation of a library of “smartprobes” designed to label a range of cells, from pathogens to host immune cells. These probes emit a fluorescent light only upon interaction with their specific target such as bacteria, thereby lighting up these cells to be detected with our fibre-based imaging system. Our ability to image pathogens in patient’s lungs will allow us to determine what treatment is best for the individual, promoting a more personalised approach to medical treatment. What’s more, by labelling immune cells as well as bacteria, we will be able to image this interaction between host and pathogen, identifying any possible failures in a patient’s immune system.
Having chosen a related PhD here in Edinburgh, OPTIMA have welcomed me into their programme and allowed me to gain a unique PhD experience I’d struggle to find anywhere else.